3-33825327-A-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013374.6(PDCD6IP):c.603A>T(p.Leu201Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,599,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

PDCD6IP
NM_013374.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Publications

3 publications found

Variant links:

Genes affected

PDCD6IP (HGNC:8766): (programmed cell death 6 interacting protein) This gene encodes a protein that functions within the ESCRT pathway in the abscission stage of cytokinesis, in intralumenal endosomal vesicle formation, and in enveloped virus budding. Studies using mouse cells have shown that overexpression of this protein can block apoptosis. In addition, the product of this gene binds to the product of the PDCD6 gene, a protein required for apoptosis, in a calcium-dependent manner. This gene product also binds to endophilins, proteins that regulate membrane shape during endocytosis. Overexpression of this gene product and endophilins results in cytoplasmic vacuolization, which may be partly responsible for the protection against cell death. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. Related pseudogenes have been identified on chromosome 15. [provided by RefSeq, Jan 2012]

PDCD6IP Gene-Disease associations (from GenCC):

microcephaly 29, primary, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

PDCD6IP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22184908).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013374.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDCD6IP	NM_013374.6	MANE Select	c.603A>T	p.Leu201Phe	missense	Exon 5 of 18	NP_037506.2
PDCD6IP	NM_001162429.3		c.603A>T	p.Leu201Phe	missense	Exon 5 of 18	NP_001155901.1	Q8WUM4-2
PDCD6IP	NM_001256192.2		c.603A>T	p.Leu201Phe	missense	Exon 5 of 6	NP_001243121.1	Q8WUM4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDCD6IP	ENST00000307296.8	TSL:1 MANE Select	c.603A>T	p.Leu201Phe	missense	Exon 5 of 18	ENSP00000307387.3	Q8WUM4-1
PDCD6IP	ENST00000457054.6	TSL:1	c.603A>T	p.Leu201Phe	missense	Exon 5 of 18	ENSP00000411825.2	Q8WUM4-2
PDCD6IP	ENST00000965906.1		c.603A>T	p.Leu201Phe	missense	Exon 5 of 19	ENSP00000635965.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000213

AC:

AN:

234318

AF XY:

0.0000237

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000373

AC:

AN:

1447760

Hom.:

Cov.:

AF XY:

0.0000375

AC XY:

AN XY:

719812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32444

American (AMR)

AF:

0.00

AC:

AN:

40254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25528

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000460

AC:

AN:

1108694

Other (OTH)

AF:

0.0000334

AC:

AN:

59892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

Eigen

Benign

-0.12

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.011

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

1.9

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Benign

0.44

Sift4G

Benign

0.61

Polyphen

0.28

Vest4

0.58

MutPred

0.53

Gain of methylation at K202 (P = 0.0277)

MVP

0.58

MPC

0.36

ClinPred

0.18

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.040

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over